Neurodevelopment in Urban Environments: Role of Exposure to Ambient Air Pollution

描述（由申请人提供）：美国城市中不断增长的儿童暴露于城市环境中存在的各种神经毒素中，这些毒素可能会损害他们正在发育的大脑。在过去十年中，环境卫生科学家已经获得了令人信服的数据，说明暴露于道路交通排放（或交通空气污染[TAP]）的当今空气污染物（包括城市环境中的颗粒物和臭氧）的动物和人类的神经毒性。实验动物模型表明，早期接触这些城市空气污染物会导致记忆障碍和长期的神经行为改变。与神经毒理学文献一致，来自横断面和纵向流行病学研究的先前数据显示，学龄或更小的儿童接触TAP会产生广泛的不良神经认知效应（包括低智商）。然而，目前尚不清楚tap介导的不良神经认知效应是否会持续到以后的生活，可能会影响青少年和年轻人的学习成绩和教育成就。虽然毒理学家已经发现了空气污染在前额叶和海马体中引起神经毒性的明确证据，但流行病学研究尚未证实高级皮层控制功能（例如，执行功能[EFs]；情绪调节）是不良暴露对神经发育影响的神经心理介质。以前的研究对暴露于神经毒性TAP和城市儿童通常经历的社会压力源所导致的联合逆境的可能性提供的见解很少。为了解决这些知识差距，本应用程序的主要目标是：(1)为城市环境中神经发育的计划长期研究生成所需的初步数据和基础设施；(2)建立一个概念框架，阐明暴露于城市空气污染物导致认知障碍和长期社会经济后果的神经心理学途径。具体而言，我们提出了一项纵向研究，该研究建立在正在进行的（2000年起）和特征明确的南加州城市双胞胎队列（R01MH058354）的基础上，对学龄（9-10岁）到年轻人（19-23岁）的神经心理功能和结果进行了全面的数据评估。该应用程序利用正在进行的儿童健康研究中独特的、前瞻性收集的环境数据和资源，能够估计早期生活（1990年以后）对空气污染的暴露情况，并详细描述青少年时期城市内TAP暴露情况。从心理健康研究中的两个理论模型（认知脆弱性-应激反应和情绪失调）出发，我们将检验情绪/情绪调节及其发展轨迹是TAP暴露对认知能力和社会经济成就的后续不利影响的中心目标和神经心理介质的假设。该项目的成功实施将极大地推动城市环境中发育神经科学这一新兴领域的发展。

DESCRIPTION (provided by applicant): The growing population of children in American cities is exposed to various neurotoxins present in urban environments which may damage their developing brains. Over the last decade, environmental health scientists have generated compelling data on neurotoxicity in animals and humans exposed to present-day air pollutants from road traffic emissions (or traffic air pollution [TAP]), including particulate matter and ozon in urban environments. Experimental animal models have demonstrated that early life exposures to these urban air pollutants result in memory impairment and long-term neurobehavioral changes. Consistent with neurotoxicological literature, previous data from both cross-sectional and longitudinal epidemiologic studies showed a wide range of adverse neurocognitive effects (including low IQ) associated with TAP exposure in school-aged or younger children. However, it remains unclear whether TAP-mediated adverse neurocognitive effects persist into later life possibly affecting academic performance and educational attainment in adolescents and young adults. Although toxicologists have revealed clear evidence of air pollution-induced neurotoxicity in the prefrontal lobe and hippocampus, epidemiologic studies have not yet examined higher cortical control functions (e.g., executive functions [EFs]; emotion regulation) as neuropsychological mediators of the adverse exposure-effects on neurodevelopment. Previous studies only provided very little insight on the likelihood of joint adversities resulting from exposures to both neurotoxic TAP and social stressors commonly experienced by urban-dwelling children. To address these knowledge gaps, the primary objectives of this application are to: (1) generate preliminary data and infrastructure needed for a planned long-term study on neurodevelopment in urban environments; and (2) develop a conceptual framework to elucidate neuropsychological pathways contributing to impaired cognition and long-term socioeconomic consequences of exposures to urban air pollutants. Specifically, we propose a longitudinal study built on an ongoing (2000- onwards) and well-characterized urban-dwelling Southern California Twin Cohort (R01MH058354) with comprehensive data on neuropsychological functions and outcomes assessed from school-age (aged 9-10) to young adults (aged 19-23). This application leverages the unique, prospectively-collected environmental data and resources of the ongoing Children's Health Study, enabling the estimation of early life (1990-onward) exposure to air pollution and detailed characterization of intra-urban TAP exposure during adolescents. Drawing from two theoretical models (cognitive vulnerability-stress response and emotional dysregulation) in mental health research, we will test the hypothesis that EFs/emotion regulation and their developmental trajectories serve as both the central target and neuropsychological mediators of subsequent adverse effects of TAP exposure on cognitive abilities and socioeconomic attainment. The successful performance of this project may greatly advance the emerging field of developmental neurosciences in urban environments.